(4S)-6a-(2,3-difluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazole → ((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

(4S)-6a-(2,3-difluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazole (3.16 g) was dissolved in acetic acid (20 mL) and the reaction mixture cooled to 0° C. Zinc (5.0 g) was added, and the reaction was allowed to warm and stir at RT for 20 h. The reaction mixture was then diluted with EtOAc (50 mL) and filtered through Celite®, washing with a further 100 mL of EtOAc. The combined organic portions were evaporated, dissolved in CHCl3 (20 mL), and ammonia (28% aq., 25 mL) was added slowly. The layers were separated, and the aqueous portion was further extracted with CHCl3 (2×25 mL). The combined organic extracts were dried over anhydrous MgSO4 and evaporated to afford the title compound (3.12 g) which was used in the subsequent step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 2.93 (ddd, J=7.8, 5.1, 2.8 Hz, 1 H), 3.85 (dd, J=12.4, 5.1 Hz, 1 H), 4.03 (dd, J=9.1, 2.8 Hz, 1 H), 4.14 (dd, J=12.3, 2.7 Hz, 1 H), 4.35 (d, J=9.1 Hz, 1 H), 4.68 (quin, J=7.3 Hz, 1 H), 7.09-7.25 (m, 2H), 7.25-7.34 (m, 1H)

Provenance & Evidence